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4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by inhibiting NF-kappaB-DNA-binding activity

Gwangsoo Lee, Hee-Jun Na, Seung Namkoong, Ho Jeong Kwon, Sanghwa Han, Kwon-Soo Ha, Young-Guen Kwon, Hansoo Lee, Young-Myeong Kim
European Journal of Pharmacology 2006 December 3, 551 (1): 143-51
17027748
We here investigated the functional effect of 4-O-methylgallic acid (4-OMGA), a major metabolite of gallic acid abundant in red wine, on vascular inflammation and its action mechanism. 4-OMGA inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-alpha (TNF-alpha), resulting in the suppression of leukocyte adhesion to HUVECs. In addition, 4-OMGA inhibited the promoter activities of ICAM-1 and VCAM-1 and the activity of nuclear factor-kappaB (NF-kappaB) without affecting cytosolic IkappaB kinase (IKK) activation, inhibitor of kappaB (IkappaB) phosphorylation and degradation, and nuclear translocation of NF-kappaB. This compound did not alter nitric oxide (NO) generation, but inhibited reactive oxygen species (ROS) production in TNF-alpha-stimulated HUVECs, suggesting that NO and ROS are not involved in 4-OMGA-mediated inhibition of NF-kappaB activity. Moreover, 4-OMGA directly blocked the binding activity of NF-kappaB to its consensus DNA oligonucleotide, when pre-incubated with the nuclear extract from TNF-alpha-stimulated HUVECs, but not with the oligonucleotide alone. This inhibition was completely abolished by the addition of dithiothreitol. 4-OMGA exhibits an anti-inflammatory property by interfering with the formation of the NF-kappaB-DNA complex in the nuclei through direct and redox-sensitive interactions and may play an important role in the prevention of inflammatory responses such as the atherosclerotic process.

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